Atomoxetine, (−)-N-methyl-3-phenyl-3 (o-tolyloxy) propylamine, or a pharmaceutically acceptable salt thereof, is a highly selective and potent inhibitor of the pre-synaptic noradrenaline transporter. Bymaster et al., 2002 Neuropsychopharmacology 27 (5): 699-711. The hydrogen chloride salt of atomoxetine, atomoxetine HCI, is marketed as Strattera®, which is prescribed as oral capsules for the treatment of attention deficit hyperactivity disorder (ADHD), in children, adolescents and adults. However, the solid dosage form has a potently bitter taste combined with a strong bitter aftertaste and a numbness that results in high incidence of non-compliance and ineffective therapy. Although there are many methods to suppress the bitterness reduce numbness and bitter aftertaste of drugs in general, they are not satisfactory to mask the highly bitter and sparingly water soluble drug such as atomoxetine. See, e.g., Vishani et al., 2013 International Journal of Pharmacy and Integrated Life Sciences 1(5): 48-61. An atomoxetine oral solution (4 mg/ml) is known to have been in the subject of a Bioequivalence study in healthy adult male Japanese subjects. Nakano et al., 2016 Clin Drug Investig. doi:10.1007/s40261-016-0430-y. Atomoxetine hydrochloride is soluble in water (27.8 mg/ml at room temperature), the desire for the development of a high concentrated oral solution dosage form of atomoxetine hydrochloride is complicated by the fact that it is an intensely bitter drug and it is even more unbearable at high concentration. Deepthi Priya et al., 2011 International Journal of Advances in Pharmaceutical Research, Vol. 2: 19. Modification with sweetening agent does not solve the bitterness and the prolonged aftertaste feeling of the patient taking the liquid dosage form. Instead, taste masking of atomoxetine solution in water utilizing certain taste masking excipients such as ethanol and mannitol is not effective because these agents only add to the bitter taste of atomoxetine, making the atomoxetine solution taste even worse. To complicate the matter further, high concentrations of taste masking agents such as sweeteners, sugar alcohols and/or flavors may be necessary for masking the taste of highly bitter drugs but such high quantities may decrease sharply the solubility of even readily soluble substances. Sohi et al., 2004 Drug Dev Ind Pharm 30(5):429-48. Taste Masking Technologies in Oral Pharmaceuticals: Recent Developments and Approaches.
Thus, it is a challenge to provide an acceptable palatable liquid dosage form, especially at high concentration of atomoxetine, for children and any individuals with any disorder that is treatable with atomoxtine who have actual or anticipated difficulties in swallowing the oral capsules or liquid formulation. In particular, the numbness of the tongue that is caused by ingesting atomoxetine has not been recognized or addressed by the industry. It remains as a challenge to provide an atomoxetine oral composition that is suitable for modifying, masking, reducing and/or suppressing unpleasant bitter taste, numbness of the tongue and the strong after-taste of atomoxetine. The present disclosure surprisingly provides pharmaceutical composition of oral aqueous atomoxetine solution at high concentration that effectively taste mask the prolonged bitterness, numbness and after taste caused by concentrated liquid dosage form.